This proposal is for biomedical applications of DMF-SAWN (Digital Microfluidics - Surface Acoustic Wave Nebulization), a highly flexible lab-on-a-chip device that can be directly coupled to mass spectrometry (MS). DMF circumvents the need for time intensive labor to produce traditional micro valve networks essential in fine manipulation of fluids. Dead volume-free preparatory steps are easily integrated without the need for enclosed micro channels, which over time can clog from debris or surface adhesion build- up. In DMF, arrays of metal electrodes are patterned on a dielectric surface and then treated with a hydrophobic layer. DMF can manipulate a greater range of volumes (nL-mL) than micro channel-based fluidics and offers streamlined multi-step sample processing such as, but not limited to extraction, purification, reconstitution, and digestion. Because the mechanism of DMF relies on a dielectric substrate, this offers a unique opportunity to couple to MS using a recently developed planar ionization technique called surface acoustic wave nebulization (SAWN). The advantages SAWN over ESI: (1) like DMF it is planar allowing the two to be readily coupled without expert knowledge of capillary based fluidics, (2) absence of the high DC voltage used in ESI SAWN produces higher signal / noise due to the elimination of redox chemistry products, (3) droplet size is inversely proportional to applied frequency allowing droplet size to be tailore to suit the need, and (4) it may be operated in a discontinuous mode allowing nanoliter-volume samples to be analyzed. Completion of this proposal will results in an MS ion source product incorporating a lab-on-a-chip. The target market is mass spectrometry, primarily for biomedical research and clinical diagnostics.